Spider Toxin Peptide Lycosin-I Functionalized Gold Nanoparticles for in vivo Tumor Targeting and Therapy

Abstract

Cell penetrating peptides (CPPs) are commonly utilized for intracellular delivery of functional materials to circumvent biomembrane barrier. However, further application of CPPs is hindered by lacking selectivity toward targeted cells. The spider venom peptide, lycosin-I, is a CPP with potent cytotoxicity to cancer cells, which might enable lycosin-I to deliver functional materials into cancer cells selectively. In this study, we demonstrated that the lycosin-I-conjugated spherical gold nanoparticles (LGNPs) not only exhibited efficient cellular internalization efficiency toward cancer cells but also displayed unprecedented selectivity over noncancerous cells. Although LGNPs were removed from the living circulatory system via reticuloendothelial system-dominant clearance modes without noticeable adverse effects to animals, they actually displayed active tumor-targeting effects and efficient accumulation in tumors in vivo. Furthermore, the potential application of this platform for cancer therapy was explored by lycosin-I-conjugated gold nanorods (LGNRs). LGNRs exhibited selective intracellular translocation towards cancer cells and efficient photothermal effect under near infrared (NIR, 808 nm) irradiation, which consequently killed cancer cells in vitro and in vivo effectively. Therefore, the established LGNPs and LGNRs possessed great potential in cancer-targeting delivery and photothermal therapy.

Cell-Penetrating Peptides Derived from Animal Venoms and Toxins

“…Owing to the cell penetration and antitumor activities, lycosin-I was used to functionalize gold nanoparticles, to target and penetrate tumors, as confirmed in vitro and in vivo with different tumor cell lines and a mouse xenograft tumor model, respectively. Moreover, as this spider venom peptide preferentially accumulated in tumor cells and tissues, lycosin-I functionalized gold nanoparticles were efficiently used to kill cancer cells by the photothermal conversion effect under near-infrared irradiation [ 88 ]. Notably, the substitution of all Lys residues in lycosin-I peptide with Arg resulted in the R-lycosin-I (Ac-RGWFRAMRSIARFIARERLREHL-amide), which displayed improved anticancer activity and cellular penetrability against solid tumor cells, as assessed by employing unlabeled peptides and fluorescent-labeled analogs, prepared by conjugation with cyanine 5 (Cy5-lycosin-I) and FITC (FITC-R-lycosin-I) [ 89 ].…”

Spider venom peptides as potential drug candidates due to their anticancer and antinociceptive activities

“…Based on its characteristics mentioned above, lycosin- I is recognized as a cell-penetrating peptide that can be used for the intracellular delivery of functional materials to circumvent the biomembrane barrier by conjugating with spherical gold nanoparticles. This conjunction will provide a stable, efficient and higher selective platform to diagnose and treat cancers correctly in the future [6, 37].…”

C7 peptide inhibits hepatocellular carcinoma metastasis by targeting the HGF/c-Met signaling pathway

“…To further confirm whether the C7 peptide actually inhibits the metastasis of hepatocellular carcinoma cells, we designed orthotopic xenograft models. The majority of research papers have used subcutaneous xenograft models to evaluate the effect of drugs, 38 but we have used orthotopic xenograft models that are more capable of modeling and can better simulate the tumor metastasis process in vivo. 39 HCCLM3 cells first formed a tumor in the liver and then metastasized to the lungs through the blood vessels; subsequently, the C7 peptide attenuated this process.…”